Viral tools for studying NG2 cells

用于研究 NG2 细胞的病毒工具

• 批准号: 8537790
• 负责人: Shaoyu Ge
• 金额: $ 18.17万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8537790
• 关键词: Adult; Biochemical; Brain; CSPG4 gene; Cell Lineage; Cell physiology; Cell surface; Cells; Chondroitin Sulfate Proteoglycan; Communities; Demyelinations; Deposition; Development; Differentiation Antigens; Genes; Goals; Homeostasis; Injury; Life; Location; Mus; Myelin; NG2 antigen; Neuroglia; Neurons; Oligodendroglia; Paper; Peripheral Nervous System; Plasmids; Population; Proliferating; Property; Proteins; Publishing; RNA Interference; Retroviral Vector; Retroviridae; Rodent; Role; Site; Slice; Spinal Cord; Spinal cord injury; Stem cells; Subfamily lentivirinae; Synapses; Viral; Viral Vector; Virus; base; cell type; electrical property; in vivo; injured; mature animal; mutant; novel; oligodendrocyte precursor; optogenetics; precursor cell; repository; response; tool; vector

DESCRIPTION (provided by applicant): Oligodendrocytes, the myelin forming cells of the CNS, develop from identified precursor cells known alternately as oligodendrocyte progenitor cells (OPCs), polydendrocytes, or NG2 cells. These cells appear about midgestation in rodents at specific locations within the developing CNS, migrate extensively, proliferate as they migrate, and then slowly differentiate into myelin-forming cells. Surprisingly, a large fraction of the OPC population fails to fully differentiate and persists throughout the adult CNS as a slowly dividing cell that can be considered an fourth glial cell type. The functions of these adult OPCs are not well understood, in part, because of their unusual mixture of glial and neuronal properties. Major questions remain regarding 1) the phenotypic plasticity of these cells in developing and adult animals and after injury and 2) the role of electrical excitability in OPC development and function. The goal of this proposal is to develop new viral-based tools for analyzing the development and properties of NG2+ OPCs. Our strategy takes advantage of the availability of cell-type specific inducible cre mouse driver lines and recently developed "flip" vectors in which tandem mutant loxP sites allow for inversion of selected genes from an anti-sense to sense orientation. This strategy allows for temporal control of the expression of marker antigens, functional proteins and RNAi. The tools to be developed here can be used widely to study other glial cell types within the central and peripheral nervous system.

描述（由申请人提供）：少突胶质细胞（CNS的髓鞘形成细胞）由经鉴定的前体细胞（称为少突胶质细胞祖细胞（OPC）、多突胶质细胞或NG2细胞）发育而来。这些细胞出现在啮齿类动物的妊娠中期，位于发育中的CNS内的特定位置，广泛迁移，随着迁移而增殖，然后缓慢分化为髓鞘形成细胞。令人惊讶的是，大部分OPC群体未能完全分化，并在整个成年CNS中持续存在，作为缓慢分裂的细胞，可以被认为是第四种神经胶质细胞类型。这些成人OPCs的功能还不清楚，部分原因是它们具有神经胶质和神经元特性的不寻常混合物。主要问题仍然是1）这些细胞在发育和成年动物中以及损伤后的表型可塑性和2）电兴奋性在OPC发育和功能中的作用。该提案的目标是开发新的基于病毒的工具，用于分析NG2+ OPCs的开发和特性。我们的策略利用了细胞类型特异性诱导型cre小鼠驱动系和最近开发的“翻转”载体的可用性，其中串联突变loxP位点允许将所选基因从反义方向反转为有义方向。这种策略允许暂时控制标记抗原、功能蛋白和RNA干扰的表达。这里开发的工具可以广泛用于研究中枢和外周神经系统内的其他胶质细胞类型。